ArticleHypertension (Dallas, Tex. : 1979)2020
Endothelial Sphingolipid De Novo Synthesis Controls Blood Pressure by Regulating Signal Transduction and NO via Ceramide.
Article in Hypertension (Dallas, Tex. : 1979), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 58 citations in OpenAlex.
- Hypertensive stretch regulates endothelial cell inflammation and apoptosis through ceramide metabolism.American journal of physiology. Cell physiology · 2026Article
- Lipid Cargo of Small Extracellular Vesicles as a Novel Contributor to Cardiovascular Diseases.International journal of molecular sciences · 2026Review
- Sphingolipids and Atherosclerosis.Current atherosclerosis reports · 2026Review
- Review
- Common Biomarkers of Endothelial Dysfunction Across Highly Prevalent Diseases with Cardiovascular Risk: Functional Characterization and Prognostic Implications.International journal of molecular sciences · 2026Article
- Serum Lipidomic Profile Signature of Active Acromegaly and Relationships to Cardiovascular Disease.International journal of molecular sciences · 2026Article
- The Role of Ceramides in Metabolic and Cardiovascular Diseases.Journal of cardiovascular development and disease · 2026Review
- Sphingolipid Metabolism: A Pathological Hub Linking Lipid Dysregulation and Chronic Inflammation in Atherosclerotic Cardiovascular Disease.Journal of inflammation research · 2026Review
- Exploring Causal Associations Between Plasma Metabolites and Sciatica: A Two-Sample Mendelian Randomization Analysis.Journal of pain research · 2026Article
- Integrated metabolomics and lipidomics reveal fatty acid dysregulation in aortic dissection independent of hypertension.Scientific reports · 2025Article
- Suppression of endothelial ceramide de novo biosynthesis by Nogo-B contributes to cardiometabolic diseases.Nature communications · 2025Article
- Sphingolipid metabolites involved in the pathogenesis of atherosclerosis: perspectives on sphingolipids in atherosclerosis.Cellular & molecular biology letters · 2025Review
- Increased serum anti-ceramide antibodies and decreased sphingosine-1-phosphate levels in patients with obstructive sleep apnea syndrome as potential markers of endothelial dysfunction.Frontiers in molecular biosciences · 2025Article
- Ceramides as Biomarkers of Cardiovascular Diseases and Heart Failure.Current heart failure reports · 2024Review
- Emerging Roles for Sphingolipids in Cardiometabolic Disease: A Rational Therapeutic Target?Nutrients · 2024Review
- Emerging role of sphingolipids and extracellular vesicles in development and therapeutics of cardiovascular diseases.International journal of cardiology. Heart & vasculature · 2024Review
- Ying and Yang of Ceramide in the Vascular Endothelium.Arteriosclerosis, thrombosis, and vascular biology · 2024Review
- Rewiring Endothelial Sphingolipid Metabolism to Favor S1P Over Ceramide Protects From Coronary Atherosclerosis.Circulation research · 2024Article
- Lysophosphatidic Acid-Mediated Inflammation at the Heart of Heart Failure.Current cardiology reports · 2024Review
- Reticulon 3 regulates sphingosine-1-phosphate synthesis in endothelial cells to control blood pressure.MedComm · 2024Article
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 3 countries.
Funding
Abstract
Ceramides are sphingolipids that modulate a variety of cellular processes via 2 major mechanisms: functioning as second messengers and regulating membrane biophysical properties, particularly lipid rafts, important signaling platforms. Altered sphingolipid levels have been implicated in many cardiovascular diseases, including hypertension, atherosclerosis, and diabetes mellitus-related conditions; however, molecular mechanisms by which ceramides impact endothelial functions remain poorly understood. In this regard, we generated mice defective of endothelial sphingolipid de novo biosynthesis by deleting the Sptlc2 (long chain subunit 2 of serine palmitoyltransferase)-the first enzyme of the pathway. Our study demonstrated that endothelial sphingolipid de novo production is necessary to regulate (1) signal transduction in response to NO agonists and, mainly via ceramides, (2) resting eNOS (endothelial NO synthase) phosphorylation, and (3) blood pressure homeostasis. Specifically, our findings suggest a prevailing role of C16:0-Cer in preserving vasodilation induced by tyrosine kinase and GPCRs (G-protein coupled receptors), except for Gq-coupled receptors, while C24:0- and C24:1-Cer control flow-induced vasodilation. Replenishing C16:0-Cer in vitro and in vivo reinstates endothelial cell signaling and vascular tone regulation. This study reveals an important role of locally produced ceramides, particularly C16:0-, C24:0-, and C24:1-Cer in vascular and blood pressure homeostasis, and establishes the endothelium as a key source of plasma ceramides. Clinically, specific plasma ceramides ratios are independent predictors of major cardiovascular events. Our data also suggest that plasma ceramides might be indicative of the diseased state of the endothelium.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.